Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis
Authors: Izanne Roos, Stella Hughes, Gavin McDonnell, Charles B. Malpas, Sifat Sharmin, Cavit Boz, Raed Alroughani, Serkan Ozakbas, Katherine Buzzard, Olga Skibina, Anneke van der Walt, Helmut Butzkueven, Jeannette Lechner-Scott, Jens Kuhle, Murat Terzi, Guy Laureys, Liesbeth Van Hijfte, Nevin John, Pierre Grammond, Francois Grand’Maison, Aysun Soysal, Ana Voldsgaard Jensen, Peter Vestergaard Rasmussen, Kristina Bacher Svendsen, Ismael Barzinji, Helle Hvilsted Nielsen, Tobias Sejbæk, Sivagini Prakash, Morten Leif Munding Stilund, Arkadiusz Weglewski, Nadia Mubder Issa, Matthias Kant, Finn Sellebjerg, Orla Gray, Melinda Magyari, Tomas Kalincik, Jose Antonio Cabrera-Gomez, Etienne Roullet, Cees Zwanikken, Leontien Den braber-Moerland, Michael Barnett, Suzanne Hodgkinson, Justin Garber, Mark Slee, Pamela McCombe, Bruce Taylor, Richard MacDonell, Jennifer Massey, Vincent Van Pesch, Danny Decoo, Barbara Willekens, Yara Fragoso, Julie Prevost, Alexandre Prat, Marc Girard, Pierre Grammond, Catherine Larochelle, Jiwon Oh, Patrice Lalive, Claudio Gobbi, Dana Horakova, Eva Havrdova, Radek Ampapa, Guillermo Izquierdo, Sara Eichau, Jose L. Sanchez-Menoyo, Cristina Ramo-Tello, Yolanda Blanco, Albert Saiz, Sarah Besora, Vahid Shaygannejad, Elisabetta Cartechini, Matteo Diamanti, Maria Pia Amato, Daniele Spitaleri, Francesco Patti, Clara Chisari, Emanuele D'Amico, Lo Fermo Salvatore, Bassem Yamout, Samia J. Khoury, Abdullah Al-Asmi, Maria Jose Sa, Talal Al-Harbi, Rana Karabudak, Recai Turkoglu, Trevor Kilpatrick, John King, Ai-Lan Nguyen, Chris Dwyer, Mastura Monif, Lisa Taylor, Josephine Baker
Journal: JAMA Neurology (2023)

Importance Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab. Objective To evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS. Design, Setting, and Participants This was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country. Exposure Treatment with ocrelizumab or rituximab after 2015. Main outcomes and Measures Noninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups. Results Of the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). Over a pairwise censored mean (SD) follow-up of 1.4 (0.7) years, the ARR ratio was higher in patients treated with rituximab than in those treated with ocrelizumab (rate ratio, 1.8; 95% CI, 1.4-2.4; ARR, 0.20 vs 0.09; P &amp;amp;lt; .001). The cumulative hazard of relapses was higher among patients treated with rituximab than those treated with ocrelizumab (hazard ratio, 2.1; 95% CI, 1.5-3.0). No difference in the risk of disability accumulation was observed between groups. Results were confirmed in sensitivity analyses. Conclusion In this noninferiority comparative effectiveness observational cohort study, results did not show noninferiority of treatment with rituximab compared with ocrelizumab. As administered in everyday practice, rituximab was associated with a higher risk of relapses than ocrelizumab. The efficacy of rituximab and ocrelizumab administered at uniform doses and intervals is being further evaluated in randomized noninferiority clinical trials.